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OBJECTIVES: The study aimed to examine the authenticity of the often-mentioned statement that the third molar is the most frequently extracted tooth. This finding has not been shown previously in a large population-based sample. MATERIALS AND METHODS: Data comprised a nationally representative sample of 6082 panoramic radiographs taken from adults in the cross-sectional Health 2000 Survey. From the radiographs, all missing teeth were recorded. Information on congenital agenesis of individual teeth was retrieved from two published meta-analyses. Primary outcome was the frequency of missing teeth by tooth type. Explanatory variables were age, sex, and the jaw (maxilla/mandible). Statistical analyses included χ2 test and binomial logistic regression. RESULTS: Mean age of participants (46% men, 54% women) was 53 years (SD 14.6; range 30â97 years). Missing teeth occurred more often in women than in men (P < 0.001). The third molar was most frequently missing and the canine least frequently. In the maxilla and mandible, the third molar was missing more often than each of the other tooth types up to the age of 80 years (P < 0.01). CONCLUSIONS: When considering the rates of congenital agenesis of individual teeth, it is concluded that the third molar remained the most common tooth extracted up till the age of 80 years. CLINICAL RELEVANCE: The third molar is the most common target for extraction, but also the most common tooth associated with malpractice claims, and therefore, calls for skills, adequate equipment, and other resources for a successful extraction.
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Dente Serotino , Radiografia Panorâmica , Extração Dentária , Humanos , Masculino , Feminino , Dente Serotino/diagnóstico por imagem , Dente Serotino/anormalidades , Estudos Transversais , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Extração Dentária/estatística & dados numéricos , Anodontia/diagnóstico por imagem , Anodontia/epidemiologiaRESUMO
OBJECTIVE: Vascular anomalies are often associated with hypertrophy and asymmetry of soft tissues and bony structures. The aim of this retrospective cross-sectional radiographic study was to evaluate dental maturation and development in patients with facial vascular anomalies and congenital infiltrating lipomatosis. DESIGN: A sample of 342 patients with different vascular anomalies or congenital infiltrating lipomatosis involving the head and neck area was narrowed down to 31 patients with dental panoramic radiographs taken in the mixed dentition. A control group of 172 age-matched healthy subjects was used. Individual permanent teeth were given a maturation score from 1 to 12 and alveolar eruption stage according to Haavikko et al. 1970. The laterality of the anomaly was noted if applicable. Differences in dental development between affected and unaffected sides were recorded. RESULTS: The study data included both syndromic and non-syndromic vascular anomalies as well as congenital infiltrating lipomatosis and segmental odontomaxillary dysplasia. Teeth on the side of the anomaly were more developed and the eruption of teeth was accelerated with canines, premolars and second molars being most affected. Interestingly all the patients with Sturge-Weber syndrome (n = 4) and infiltrating lipomatosis (n = 2) showed accelerated dental maturation of multiple permanent teeth on the side of the anomaly. Hypodontia, dental root resorption and macrodontia were also found. CONCLUSIONS: Accelerated development and eruption of permanent teeth unilaterally in patients with vascular anomalies and congenital infiltrating lipomatosis may have a significant impact on the developing occlusion and should be thus followed by an orthodontist.
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BACKGROUND/RATIONALE: Systematic reviews on the effects of pacifiers on occlusion have highlighted the need for quality RCTs. TRIAL DESIGN: Single region, three parallel-armed, prospective, randomized controlled trial. OBJECTIVES: To investigate the correlations between early childhood non-nutritive sucking habits and malocclusion. Specifically to test whether the use of a study pacifier has differing effects compared to other pacifiers and control, and whether the duration of pacifier use or digit sucking influence the occlusion. PARTICIPANTS: The subjects were firstborn children, born in 2008 in Vantaa, Finland. INTERVENTION: One-third of participants were offered study pacifiers, free of charge, from birth up to 2 years of age. The history of the subjects' sucking habits, including pacifier use was screened in a questionnaire at the age of 2 years, and clinical examinations were performed at the age of 7 years. In addition, the subjects were divided into groups that were equally matched regarding their mother's level of education. OUTCOMES: Posterior crossbite, anterior crossbite, overjet, deep bite, open bite, and crowding. RANDOMIZATION METHOD: Three districts were randomly allocated to three study groups by drawing lots. BLINDING: It was not possible to blind the clinicians or parents from the intervention. Blinding during data analysis was performed. RESULTS: From the original cohort of 2715 children born in the town of Vantaa, 1911 were excluded and 353 were lost to follow-up. The remaining 451 children were divided into three groups according to the use of pacifiers. The prevalence of posterior crossbite at the age of 7 years was higher if a non-study pacifier had been used (Pâ =â .005) even when matched for the mother's level of education (Pâ =â .029). The prevalence of posterior crossbite was higher if the pacifier habit had continued for 12 months or more compared to 11 months or less, 7% and 1%, respectively, (Pâ =â .003). Digit sucking for 12 months or more was associated with crowding (Pâ =â .016). The prevalence of crossbite in the study pacifier group was less than in control pacifiers. HARMS: No adverse harms were reported other than effects on the dentition. CONCLUSION: The use of pacifiers is associated with the posterior crossbite, especially if their use continues for a year or more. Parents/guardians should be advised to stop the use or reduce the use of pacifiers to a minimum after their child's first birthday. TRIAL REGISTRATION: ClinicalTrials.gov NCT01854502.
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Sucção de Dedo , Má Oclusão , Chupetas , Comportamento de Sucção , Humanos , Chupetas/efeitos adversos , Feminino , Masculino , Sucção de Dedo/efeitos adversos , Lactente , Estudos Prospectivos , Pré-Escolar , Criança , Mordida Aberta/etiologia , Finlândia , Fatores de TempoRESUMO
We aimed to characterize the genetic basis and craniofacial and dental features of Finnish patients with Axenfeld-Rieger syndrome (ARS). Mutational analyses of seven patients in five families were performed by sequencing or comparative genomic hybridization. Phenotypic analysis was based on both clinical and radiographic examinations, as well as on medical data. Lateral cephalometric radiographs of five patients were analysed using Viewbox 3.1-Cephalometric Software. The cephalometric values were compared to Finnish population-standard values of the same age and gender. Two frameshift mutations and three whole gene deletions were detected in five families. Class III skeletal relationship with retrognathic maxilla and mildly retrognathic mandible were detected in all five patients studied. Significant differences compared with the control values were in SNA (P = .0014), ANB (P = .0043) and SNB angles (P = .013). Five patients had anterior crossbite. Six patients showed tooth agenesis. The average number of missing teeth (third molars excluded) was 9 (range 0-15). The tooth agenesis rate was 52% in maxilla and 26% in mandible. Maxillary central and lateral permanent incisors were most often missing (rate 71% equally) while no one lacked canines or first molars in mandible. Two patients had a supernumerary mandibular permanent incisor. Six patients had either taurodontic and/or single-rooted molars. Our results suggest that class III skeletal relationship with maxillary and mandibular retrognathism, anterior crossbite, maxillary incisor agenesis and taurodontic, even pyramidal, roots are common determinants of ARS caused by PITX2 mutations.
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Anodontia , Má Oclusão , Humanos , Hibridização Genômica Comparativa , Anodontia/diagnóstico por imagem , Anodontia/genética , Mutação , MaxilaRESUMO
BACKGROUND: Studies on the association between malocclusion and temporomandibular joint disorder (TMD) have reported conflicting results. OBJECTIVES: To determine the impact of malocclusion and orthodontic treatment on symptoms of TMD. METHODS: At 12 years, 195 subjects fulfilled a questionnaire regarding TMD symptoms and participated in an oral examination including preparation of dental casts. The study was repeated at ages 15 and 32. The occlusions were assessed by applying the Peer Assessment Rating (PAR) Index. Associations between the changes in PAR scores and TMD symptoms were analysed with the chi-square test. A multivariable logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) of TMD symptoms at 32 years predicted by sex, occlusal traits and orthodontic treatment history. RESULTS: One in three subjects (29%) was orthodontically treated. Sex was associated with more self-reported headaches by females at 32 years (OR 2.4, 95% CI 1.05-5.4; p = .038). At all time points, any crossbite was significantly associated with greater odds for self-reported temporomandibular joint (TMJ) sounds at 32 years (OR 3.5, 95% CI 1.1-11.6; p = .037). More specifically, association occurred with posterior crossbite (OR 3.3, 95% CI 1.1-9.9; p = .030). At 12 and 15 years, boys whose PAR score increased were more likely to develop TMD symptoms (p = .039). Orthodontic treatment had no impact on the number of symptoms. CONCLUSIONS: Presence of crossbite may increase the risk of self-reported TMJ sounds. Also, longitudinal changes in occlusion may have an association with TMD symptoms while orthodontic treatment is not associated with the number of symptoms.
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Má Oclusão , Transtornos da Articulação Temporomandibular , Masculino , Feminino , Humanos , Estudos Prospectivos , Ortodontia Corretiva , Má Oclusão/complicações , Má Oclusão/terapia , Transtornos da Articulação Temporomandibular/complicações , Oclusão DentáriaRESUMO
OBJECTIVES: To analyse the differences between dental age and chronological age and dental anomalies in individuals with Van der Woude syndrome (VWS) and compare with non-syndromic cleft palate (NSCP) and non-cleft controls. MATERIALS AND METHODS: In total, 204 oral panoramic radiographs (118 girls and 86 boys) consisting of 51 VWS patients (age xÌ = 8.17 ± 1.34 years), 51 NSCP patients (age xÌ = 8.09 ± 1.41 years), and 102 normative non-cleft children (age xÌ = 8.62 ± 1.24 years) were collected. Dental stages were assessed by the Demirjian method, with the local dental maturity index as reference. Dental anomalies including agenesis were investigated. Statistical differences were determined by One-way ANOVA and regression. Repeatability was calculated by an intra-class correlation test and 95% confidence interval. RESULTS: The difference between dental age and chronological age of the VWS group (0.12 years) and the NSCP group (0.09 years) was significantly lower than the non-cleft group (0.40 years) (P = 0.002). There was no significant difference between the VWS and NSCP groups (P = 0.885). Hypodontia was more prevalent in both the VWS group (37.25%, P = 0.0001) and the NSCP group (19.60%, P = 0.035) compared with the non-cleft group (5.88%). The odds for hypodontia in the VWS group were approximately double compared with the NSCP group. In VWS patients, the most commonly missing teeth were the permanent second premolars and the maxillary permanent laterals incisors. Peg-shaped teeth had a prevalence of 13.70% in VWS patients. CONCLUSIONS: In VWS and NSCP patients compared with non-cleft children, the difference in dental age compared with chronological age decreased. Hypodontia occurs at a high prevalence in VWS and NSCP patients compared with non-cleft children.
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Anormalidades Múltiplas , Fenda Labial , Fissura Palatina , Criança , Fenda Labial/diagnóstico por imagem , Fissura Palatina/complicações , Fissura Palatina/diagnóstico por imagem , Cistos , Feminino , Humanos , Lactente , Lábio/anormalidades , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVES: To analyse prevalence, pattern, and severity of taurodontism in individuals with Van der Woude syndrome (VWS) exhibiting cleft palate and compare with aged-matched non-syndromic cleft palate (NSCP) and non-cleft controls. MATERIALS AND METHODS: One hundred and seventy-eight dental panoramic tomographs (DPTs) (105 girls and 73 boys) consisting of 42 VWS patients (x¯=8.55±1.02 years), 42 NSCP patients (x¯=8.59±1.02 years), and 94 normative non-cleft children (x¯=8.79±1.16 years) were assessed and their first permanent molars evaluated. Measurement 3 of the taurodontism index developed by Shifman and Chanannel with the Tulensalo modification was used. Prevalence, pattern, and severity were compared between groups. Statistical differences were determined by one-way analysis of variance and Fisher test. Repeatability was calculated by Cohens Kappa test. RESULTS: The prevalence of taurodontic molars was 59.5% in VWS, 45.2% in NSCP, and 26.6% in non-cleft controls. The prevalence and severity of taurodontism in VWS and NSCP were significantly higher than in non-cleft children in all first permanent molars. There was no significant difference in prevalence and severity between VWS and NSCP. The odds for having taurodontism in the VWS group was approximately double compared to the NSCP group. Most of the taurodontic molars showed hypotaurodontism and taurodontism occurred bilaterally more frequently than unilaterally. CONCLUSION: This study shows a higher prevalence of taurodontism in VWS and NSCP. Most taurodontic molars are hypotaurodontic and most occur bilaterally.
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Fenda Labial , Fissura Palatina , Anormalidades Múltiplas , Idoso , Criança , Fenda Labial/diagnóstico por imagem , Fissura Palatina/diagnóstico por imagem , Fissura Palatina/epidemiologia , Cistos , Cavidade Pulpar/anormalidades , Feminino , Humanos , Lábio/anormalidades , Masculino , Dente Molar/diagnóstico por imagem , Anormalidades DentáriasRESUMO
Aim: To investigate the long-term (≥15 years) post-treatment (Tx) occlusal changes and outcome quality after Class II:1 Tx. Subjects and Methods: Herbst-MBA Tx had been performed at age 12.8 ± 2.7 years in 119 patients. A recall was conducted and study models from before and after active Tx, after retention as well as after recall were evaluated using standard occlusal variables and the PAR index. These data were compared to 31 untreated Class I controls. Results: 52 out of 119 patients could be located and participated at 33.6 ± 3.1 years. Compared to the 67 patients who did not participate in the recall, the pre- and post-Tx occlusal data of the participants did not differ systematically; however, the PAR scores were higher by 3.0-4.7 points at all times. Pre-Tx, the mean values of the 52 participants were: PAR = 27.2 ± 7.6, Class II molar relationship (MR) = 0.7 cusp widths (cw), overjet = 8.2 mm, overbite = 4.1 mm. After Tx, the PAR score was 3.4 ± 2.2. A Class I MR (0.0 ± 0.1 cw) with normal overjet (2.3 ± 0.7 mm) and overbite (1.3 ± 0.7 mm) existed. At recall, a mild PAR score increase to 8.2 ± 5.5 points had occurred; this was mainly due to increased overjet and overbite values (3.6 ± 1.1 and 2.8 ± 1.6 mm) while the MR was stable (0.0 ± 0.2 cw). For all these variables, similar findings were made in the untreated controls. Conclusion: The occlusal outcome of Class II:1 Tx showed very good long-term stability. While mild changes occur post-Tx, the long-term result is similar to untreated Class I controls.
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Má Oclusão Classe II de Angle/terapia , Adolescente , Cefalometria/métodos , Criança , Oclusão Dentária , Feminino , Seguimentos , Humanos , Masculino , Má Oclusão Classe I de Angle/patologia , Má Oclusão Classe II de Angle/patologia , Aparelhos Ortodônticos Funcionais , Ortodontia Corretiva/instrumentação , Ortodontia Corretiva/métodos , Sobremordida/terapia , Resultado do TratamentoRESUMO
Aim: To investigate the outcome quality and the long-term (≥15 years) post-treatment (Tx) changes after Class II:2 Herbst-multibracket appliance (MBA) Tx. Subjects and Methods: In this longitudinal observational study, a recall of Class II:2 patients who had been treated by a Herbst-MBA during adolescence was conducted. Study models from before and after active Tx, after retention and after recall were assessed using standard occlusal variables and the peer assessment rating index (PAR). These data were compared to historical untreated Class I controls. Results: Twenty out of 33 patients (61%) could be located and participated at age 33.9 ± 2.7 years. When comparing their data to the 13 patients who did not participate, the pre- and post-Tx occlusal findings did not differ systematically; however, the PAR scores of the non-participants were by 3.3-8.2 points higher at all times and the non-participants were 2.1-2.5 years older. Pre-Tx at age 14.4 ± 2.7 years, the participants showed the following mean values: PAR = 15.0 ± 7.0, Class II molar relationship (MR) = 0.8 ± 0.3 cusp widths (cw), overbite = 5.3 ± 1.3 mm. After Tx, a PAR score of 2.9 ± 1.3 and a super Class I MR (-0.1 ± 0.1 cw) with normal overbite (1.2 ± 0.8 mm) existed. At recall, a PAR score increase to 5.9 ± 3.6 points had occurred, mainly caused by an increase of overbite to 2.5 ± 1.5 mm. The average MR remained Class I (0.0 ± 0.2 cw). For all variables, the untreated controls exhibited similar findings. Conclusion: The occlusal outcome of Class II:2 Herbst-MBA Tx exhibited very good long-term stability. While mild post-Tx changes occurred, the long-term findings are similar to untreated Class I controls.
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Má Oclusão Classe II de Angle/terapia , Aparelhos Ortodônticos Funcionais , Ortodontia Corretiva/instrumentação , Adolescente , Cefalometria/métodos , Feminino , Humanos , Estudos Longitudinais , Masculino , Má Oclusão Classe II de Angle/patologia , Modelos Dentários , Contenções Ortodônticas , Sobremordida/patologia , Sobremordida/terapia , Resultado do TratamentoRESUMO
Hypertrophy, hyperplasia and altered mucus secretion from the respiratory submucosal glands (SMG) are characteristics of airway diseases such as cystic fibrosis, asthma and chronic bronchitis. More commonly, hyper-secretion of the nasal SMGs contributes to allergic rhinitis and upper airway infection. Considering the role of these glands in disease states, there is a significant dearth in understanding the molecular signals that regulate SMG development and patterning. Due to the imperative role of FGF signalling during the development of other branched structures, we investigated the role of Fgf10 during initiation and branching morphogenesis of murine nasal SMGs. Fgf10 is expressed in the mesenchyme around developing SMGs while expression of its receptor Fgfr2 is seen within glandular epithelial cells. In the Fgf10 null embryo, Steno's gland and the maxillary sinus gland were completely absent while other neighbouring nasal glands showed normal duct elongation but defective branching. Interestingly, the medial nasal glands were present in Fgf10 homozygotes but missing in Fgfr2b mutants, with expression of Fgf7 specifically expressed around these developing glands, indicating that Fgf7 might compensate for loss of Fgf10 in this group of glands. Intriguingly the lateral nasal glands were only mildly affected by loss of FGF signalling, while these glands were missing in Eda mutant mice, where the Steno's and maxillary sinus gland developed as normal. This analysis reveals that regulation of nasal gland development is complex with different subsets of glands being regulated by different signalling pathways. This analysis helps shed light on the nasal gland defects observed in patients with hypohidrotic ectodermal dysplasia (HED) (defect EDA pathway) and LADD syndrome (defect FGFR2b pathway).
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Ectodisplasinas/fisiologia , Glândulas Exócrinas/embriologia , Fator 10 de Crescimento de Fibroblastos/fisiologia , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/fisiologia , Transdução de Sinais/fisiologia , Animais , Ectodisplasinas/deficiência , Ectodisplasinas/genética , Ressecção Endoscópica de Mucosa , Glândulas Exócrinas/metabolismo , Glândulas Exócrinas/ultraestrutura , Feminino , Fator 10 de Crescimento de Fibroblastos/deficiência , Fator 10 de Crescimento de Fibroblastos/genética , Fator 7 de Crescimento de Fibroblastos/fisiologia , Masculino , Seio Maxilar/embriologia , Seio Maxilar/ultraestrutura , Mesoderma/metabolismo , Camundongos , Morfogênese , Mucosa Nasal/embriologia , Mucosa Nasal/ultraestrutura , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/deficiência , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genéticaRESUMO
Blepharocheilodontic (BCD) syndrome is a rare condition characterized by bilateral cleft lip and palate (BCLP), eyelid abnormalities, and oligodontia. Despite orofacial clefting and oligodontia being central features of the condition, detailed reports of dental and craniofacial characteristics are scarce. The aim of this study was to analyze the dental and craniofacial features in a group of patients with BCD syndrome (three of which were related). Cephalometric radiographic analyses were performed on BCD syndrome patients (all radiographs taken at age 8 years) and compared to 40 randomly selected age-matched controls (20 non-syndromic BCLP, 20 non-cleft). Also, we assessed clinical records, photographs, dental study casts, and dental radiographs to determine the extent and pattern of tooth agenesis, dental morphology and malocclusion. BCD syndrome patients showed a very severe skeletal III malocclusion (maxillary-mandibular sagittal discrepancy) and reduced anterior lower face measurement compared to non-syndromic BCLP and non-cleft controls (P = 0.001, P = 0.027). All patients exhibited oligodontia (mean number of missing permanent teeth 13.7, range 7-17). All patients exhibited missing upper central and lateral incisor, upper canine and premolar teeth. Variations in dental morphology included taurodontism, conical-shaped teeth, and notching of the incisal edges. All patients had a short and narrow maxilla which translated into anterior and posterior cross bites. We conclude that, in our BCD syndrome group, the craniofacial skeletal defects are more severe than patients with BCLP. The pattern of tooth agenesis is unusual as it included teeth that are normally highly resistant to agenesis, namely upper central incisor and canine teeth. © 2017 Wiley Periodicals, Inc.
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Anodontia/diagnóstico por imagem , Fenda Labial/diagnóstico por imagem , Fissura Palatina/diagnóstico por imagem , Ectrópio/diagnóstico por imagem , Face/diagnóstico por imagem , Má Oclusão/diagnóstico por imagem , Base do Crânio/diagnóstico por imagem , Anormalidades Dentárias/diagnóstico por imagem , Adulto , Anodontia/patologia , Cefalometria , Criança , Fenda Labial/patologia , Fissura Palatina/patologia , Dente Canino/diagnóstico por imagem , Dente Canino/patologia , Ectrópio/patologia , Face/patologia , Feminino , Humanos , Incisivo/diagnóstico por imagem , Incisivo/patologia , Masculino , Má Oclusão/patologia , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Maxila/diagnóstico por imagem , Maxila/patologia , Linhagem , Radiografia , Base do Crânio/patologia , Anormalidades Dentárias/patologiaRESUMO
OBJECTIVE: Remote teaching strategies have been widely adapted in recent years but their impact on dental students' learning outcomes is less well understood. The aim of this mixed-method pilot study was to examine the impact of remote teaching on undergraduate dental student's learning outcome as assessed by examination performance and student feedback in an orthodontics course. METHODS: Out of the lectures (19 in total), 10 were delivered remotely (live online lecture or video recording) and 9 as traditional classroom teaching in 2023. The course examination, completed by 47 of the 48 course participants, consisted of 38 single best answer multiple choice questions with 2 questions dedicated to each lecture topic. RESULTS: The average lecture attendance was 83% of the students enrolled in the course. Statistical analysis revealed no significant association between examination scores and the mode of teaching or the mandatory nature of the lecture (rs = -0.022, p = .897 and rs = -0.048, p = .773, respectively). However, individual students' examination scores correlated positively with the frequency of lecture attendance (rs = 0.416, p = .004). Students' preferences were in favor of blended learning approach, although notable individual differences in opinions were observed in the feedback received. CONCLUSION: The findings of this study support the hypothesis that remote teaching generates an equally good learning outcome in orthodontics as classroom lectures, as reflected by examination performance.
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In Finland the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We performed a genome-wide association study for orofacial clefts, which include CL/P and CP, in the Finnish population. We identified rs570516915, a single nucleotide polymorphism that is highly enriched in Finns and Estonians, as being strongly associated with CP ( P = 5.25 × 10 -34 , OR = 8.65, 95% CI 6.11-12.25), but not with CL/P ( P = 7.2 × 10 -5 ), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence in Finland, and the association was replicated in independent cohorts of CP cases from Finland ( P = 8.82 × 10 -28 ) and Estonia ( P = 1.25 × 10 -5 ). The risk allele of rs570516915 disrupts a conserved binding site for the transcription factor IRF6 within a previously characterized enhancer upstream of the IRF6 gene. Through reporter assay experiments we found that the risk allele of rs570516915 diminishes the enhancer activity. Oral epithelial cells derived from CRISPR-Cas9 edited induced pluripotent stem cells demonstrate that the CP-associated allele of rs570516915 concomitantly decreases the binding of IRF6 and the expression level of IRF6 , suggesting impaired IRF6 autoregulation as a molecular mechanism underlying the risk for CP.
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In Finland, the frequency of isolated cleft palate (CP) is higher than that of isolated cleft lip with or without cleft palate (CL/P). This trend contrasts to that in other European countries but its genetic underpinnings are unknown. We conducted a genome-wide association study in the Finnish population and identified rs570516915, a single nucleotide polymorphism highly enriched in Finns, as strongly associated with CP (P = 5.25 × 10-34, OR = 8.65, 95% CI 6.11-12.25), but not with CL/P (P = 7.2 × 10-5), with genome-wide significance. The risk allele frequency of rs570516915 parallels the regional variation of CP prevalence in Finland, and the association was replicated in independent cohorts of CP cases from Finland (P = 8.82 × 10-28) and Estonia (P = 1.25 × 10-5). The risk allele of rs570516915 alters a conserved binding site for the transcription factor IRF6 within an enhancer (MCS-9.7) upstream of the IRF6 gene and diminishes the enhancer activity. Oral epithelial cells derived from CRISPR-Cas9 edited induced pluripotent stem cells demonstrate that the CP-associated allele of rs570516915 concomitantly decreases the binding of IRF6 and the expression level of IRF6, suggesting impaired IRF6 autoregulation as a molecular mechanism underlying the risk for CP.